Study protocol of a randomized controlled trial evaluating home treatment with peer support for acute mental health crises (HoPe).

BACKGROUND: Home treatment (HT) is a treatment modality for patients with severe mental illness (SMI) in acute mental crises. It is frequently considered equivalent to psychiatric inpatient treatment in terms of treatment outcome. Peer Support (PS) means that people with lived experience of a mental illness are trained to support others on their way towards recovery. While PS is growing in international importance and despite a growing number of studies supporting its benefits, it is still not comprehensively implemented into routine care. The HoPe (Home Treatment with Peer Support) study investigates a combination of both - HT and PS - to provide further evidence for a recovery-oriented treatment of psychiatric patients. METHODS: In our randomized controlled trial (RCT), HT with PS is compared with HT without PS within a network of eight psychiatric clinical centers from the North, South and East of Germany. We investigate the effects of a combination of both approaches with respect to the prevention of relapse/recurrence defined as first hospitalization after randomization (primary outcome), disease severity, general functioning, self-efficacy, psychosocial health, stigma resistance, recovery support, and service satisfaction (secondary outcomes). A sample of 286 patients will be assessed at baseline after admission to HT care (data point t0) and randomized into the intervention (HT + PS) and control arm (HT). Follow-Up assessments will be conducted 2, 6 and 12 months after admission (resulting in three further data points, t1 to t3) and will be analyzed via intention-to-treat approach. DISCUSSION: This study may determine the positive effects of PS added to HT, prove additional evidence for the efficacy of PS and thereby facilitate its further implementation into psychiatric settings. The aim is to improve quality of mental health care and patients' recovery as well as to reduce the risk of relapses and hospitalizations for patients with SMI. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov: NCT04336527 , April 7, 2020.

Differences in Attitudes Toward Online Interventions in Psychiatry and Psychotherapy Between Health Care Professionals and Nonprofessionals: A Survey.

Background:Although the use of e-mental health interventions and their evaluation is already well advanced in countries such as the United States and Australia, research in this area is still in the early stages in Germany. Moreover, existing programs are used only to a small extent by patients, although physicians and therapists generally have a positive attitude toward their use. To help promote the use of online interventions in the future, an analysis of the differences in opinions and attitudes toward e-mental health interventions between health care professionals and nonprofessionals is necessary.Objective:This study aimed to examine the differences in attitudes toward online interventions between health care professionals and nonprofessionals.Methods:This study examined 92 physicians, 36 psychotherapists, and 1,353 randomly recruited nonprofessionals with the eight-item questionnaire entitled "Attitudes on telemedicine in psychiatry and psychotherapy (ATiPP)."Results:The questionnaires of n = 62 physicians, n = 37 psychotherapists, and n = 1,353 nonprofessionals were included in the analysis. Overall, nonprofessionals rate the use of telemedicine more critically than professionals. The itemwise t tests show significant differences between health care professionals and nonprofessionals on six out of eight items. The analyses of variance with post hoc tests for each single item also found differences between the groups (physicians vs. therapists vs. telephone participants vs. practice sample).Conclusion:There are significant differences in attitudes toward online interventions between professionals and nonprofessionals.

White Matter Microstructural Changes and Episodic Memory Disturbances in Late-Onset Bipolar Disorder.

Background: Bipolar disorder (BD) has been associated with distributed network disruption, but little is known on how different clinical subtypes, particularly those with an earlier and later onset of disease, are related to connectivity changes in white matter (WM) tracts. Methods: Diffusion tensor imaging (DTI) and volumetric measures were carried out in early-onset bipolar patients [(EOD) (n = 16)], late-onset bipolar disorder [(LOD)(n = 14)] and healthy controls (n = 32). We also computed ROI analysis of gray matter (GM) and white matter (WM) volumes using the regions with significant group differences in the DTI parameters. Cognitive and behavior measurements were analyzed between groups. Results: Lower fraction of anisotropy (FA) in the right hemisphere comprising anterior thalamic radiation, fornix, posterior cingulate, internal capsule, splenium of corpus callosum was observed in the LOD in comparison with EOD; additionally, lower FA was also found in the LOD in comparison with healthy controls, mostly in the right hemisphere and comprising fibers of the splenium of the corpus callosum, cingulum, superior frontal gyrus and posterior thalamic radiation; LOD also showed worse episodic memory performance than EOD; no statistical significant differences between mood symptoms, WM and GM volumes were found between BD groups. Conclusion: Even after correcting for age differences, LOD was associated with more extensive WM microstructural changes and worse episodic memory performance than EOD; these findings suggest that changes in the WM fiber integrity may be associated with a later presentation of BD, possibly due to mechanisms other than neuroprogression. However, these findings deserve replication in larger, prospective, studies.

Development of a Questionnaire to Measure the Attitudes of Laypeople, Physicians, and Psychotherapists Toward Telemedicine in Mental Health.

BACKGROUND: In the field of psychiatry and psychotherapy, there are now a growing number of Web-based interventions, mobile phone apps, or treatments that are available via remote transmission screen worldwide. Many of these interventions have been shown to be effective in studies but still find little use in everyday therapeutic work. However, it is important that attitude and expectation toward this treatment are generally examined, because these factors have an important effect on the efficacy of the treatment. To measure the general attitude of the users and prescribers toward telemedicine, which may include, for instance, Web-based interventions or interventions through mobile phone apps, there are a small number of extensive tests. The results of studies based on small groups of patients have been published too, but there is no useful short screening tool to give an insight into the general population's attitude. We have developed a screening instrument that examines such attitude through a few graded questions. OBJECTIVE: This study aimed to explore the Attitude toward Telemedicine in Psychiatry and Psychotherapy (ATiPP) and to evaluate the results of general population and some subgroups. METHODS: In a three-step process, the questionnaire, which is available in three versions (laypeople, physicians, and psychologists), was developed. Afterwards, it was evaluated by four groups: population-representative laypeople, outpatients in different faculties, physicians, and psychotherapists. RESULTS: The results were evaluated from a total of 1554 questionnaires. The sample population included 1000 laypeople, 455 outpatients, 62 physicians, and 37 psychotherapists. The reliability of all three versions of the questionnaire seemed good, as indicated by the Cronbach alpha values of .849 (the laypeople group), .80 (the outpatients' group), .827 (the physicians' group), and .855 (the psychotherapists' group). CONCLUSIONS: The ATiPP was found to be useful and reliable for measuring the attitudes toward the Web-based interventions in psychiatry and psychotherapy and should be used in different studies in this field in the future to evaluate and reflect the attitude of the participants.

Cortical thinning in bipolar disorder and schizophrenia.

Although schizophrenia (SZ) and bipolar disorder (BD) share some clinical features such as psychotic symptoms and cognitive dysfunctions, little is known about possible pathophysiological similarities between both diseases. Therefore, we investigated the potential topographical overlap and segregation of cortical thickness abnormalities in SZ and BD patients. We analyzed 3D-anatomical magnetic resonance imaging datasets with the FreeSurfer 5.1.0 software to examine cortical thickness and volumes in three groups of participants: n=34 BD patients, n=32 SZ patients and n=38 healthy controls. We observed similar bilateral cortical thickness reductions in BD and SZ patients predominantly in the pars opercularis of the inferior frontal gyrus and in the anterior and posterior cingulate. We also found disease-specific cortical reductions in the orbitofrontal cortex for BD patients and in dorsal frontal and temporal areas for SZ. Furthermore, inferior frontal gyrus cortical thinning was associated with deficits in psychomotor speed and executive functioning in SZ patients and with age at onset in both groups. Our findings support the hypothesis that thinning of the frontal cortex may represent a biological feature shared by both disease groups. The associations between cognitive deficits and the reported findings in SZ and to a lesser degree in BD patients add to the functional relevance of our results. However, further studies are needed to corroborate a model of shared pathophysiological disease features across BD and SZ.

Schizophrenia risk variants modulate white matter volume across the psychosis spectrum: evidence from two independent cohorts.

Polygenic risk scores, based on risk variants identified in genome-wide-association-studies (GWAS), explain a considerable portion of the heritability for schizophrenia (SZ) and bipolar disorder (BD). However, little is known about the combined effects of these variants, although polygenic neuroimaging has developed into a powerful tool of translational neuroscience. In this study, we used genome wide significant SZ risk variants to test the predictive capacity of the polygenic model and explored potential associations with white matter volume, a key candidate in imaging phenotype for psychotic disorders. By calculating the combined additive schizophrenia risk of seven SNPs (significant hits from a recent schizophrenia GWAS study), we show that increased additive genetic risk for SZ was associated with reduced white matter volume in a group of participants (n = 94) consisting of healthy individuals, SZ first-degree relatives, SZ patients and BD patients. This effect was also seen in a second independent sample of healthy individuals (n = 89). We suggest that a moderate portion of variance (~4%) of white matter volume can be explained by the seven hits from the recent schizophrenia GWAS. These results provide evidence for associations between cumulative genetic risk for schizophrenia and intermediate neuroimaging phenotypes in models of psychosis. Our work contributes to a growing body of literature suggesting that polygenic risk may help to explain white matter alterations associated with familial risk for psychosis.

Functional connectivity pattern during rest within the episodic memory network in association with episodic memory performance in bipolar disorder.

In this study, we sought to examine the intrinsic functional organization of the episodic memory network during rest in bipolar disorder (BD). The previous work suggests that deficits in intrinsic functional connectivity may account for impaired memory performance. We hypothesized that regions involved in episodic memory processing would reveal aberrant functional connectivity in patients with bipolar disorder. We examined 21 patients with BD and 21 healthy matched controls who underwent functional magnetic resonance imaging (fMRI) during a resting condition. We did a seed-based functional connectivity analysis (SBA), using the regions of the episodic memory network that showed a significantly different activation pattern during task-related fMRI as seeds. The functional connectivity scores (FC) were further correlated with episodic memory task performance. Our results revealed decreased FC scores within frontal areas and between frontal and temporal/hippocampal/limbic regions in BD patients in comparison with controls. We observed higher FC in BD patients compared with controls between frontal and limbic regions. The decrease in fronto-frontal functional connectivity in BD patients showed a significant positive association with episodic memory performance. The association between task-independent dysfunctional frontal-limbic FC and episodic memory performance may be relevant for current pathophysiological models of the disease.

Association between age of disease-onset, cognitive performance and cortical thickness in bipolar disorders.

OBJECTIVES: Neuroimaging studies in patients with bipolar disorder (BD) have indicated a number of structural brain changes, including reduced cortical thickness. However, the effects of the course of illness, clinical and cognitive variables on cortical thickness in BD patients have not yet been evaluated. METHODS: A total of 67 individuals (32 patients with euthymic BD and 35 healthy and age-matched controls) underwent 3D-anatomical magnetic resonance imaging (MRI). Whole-brain cortical thickness and group differences were assessed using the Freesurfer software. Course of disease variables, clinical and cognitive parameters were correlated with cortical thickness measures. RESULTS: We found reduced cortical thickness in BD patients compared with controls in the frontal and temporal lobes and in several limbic areas. We also report significant associations between cortical thickness and age of disease-onset, speed of cognitive processing, executive function and depression severity in BD patients. CONCLUSIONS: Cortical thickness reduction across frontal and limbic areas is a structural correlate of affective symptom severity and cognitive impairments in BD as well of age of disease-onset. We may assume that frontal lobe structural abnormalities are present in bipolar disorder, and might lead to dysfunctional cognitive functioning. The causality and functional relevance beyond mere correlation, however, is yet to be established. Our findings encourage further longitudinal studies in BD patients and in healthy at-risk subjects in order to discern the temporal order and development of morphological changes and clinical symptoms.

Multimodal assessments of the hippocampal formation in schizophrenia and bipolar disorder: evidences from neurobehavioral measures and functional and structural MRI.

A potential clinical and etiological overlap between schizophrenia (SZ) and bipolar disorder (BD) has long been a subject of discussion. Imaging studies imply functional and structural alterations of the hippocampus in both diseases. Thus, imaging this core memory region could provide insight into the pathophysiology of these disorders and the associated cognitive deficits. To examine possible shared alterations in the hippocampus, we conducted a multi-modal assessment, including functional and structural imaging as well as neurobehavioral measures of memory performance in BD and SZ patients compared with healthy controls. We assessed episodic memory performance, using tests of verbal and visual learning (HVLT, BVMT) in three groups of participants: BD patients (n = 21), SZ patients (n = 21) and matched (age, gender, education) healthy control subjects (n = 21). In addition, we examined hippocampal resting state functional connectivity, hippocampal volume using voxel-based morphometry (VBM) and fibre integrity of hippocampal connections using diffusion tensor imaging (DTI). We found memory deficits, changes in functional connectivity within the hippocampal network as well as volumetric reductions and altered white matter fibre integrity across patient groups in comparison with controls. However, SZ patients when directly compared with BD patients were more severely affected in several of the assessed parameters (verbal learning, left hippocampal volumes, mean diffusivity of bilateral cingulum and right uncinated fasciculus). The results of our study suggest a graded expression of verbal learning deficits accompanied by structural alterations within the hippocampus in BD patients and SZ patients, with SZ patients being more strongly affected. Our findings imply that these two disorders may share some common pathophysiological mechanisms. The results could thus help to further advance and integrate current pathophysiological models of SZ and BD.

Episodic memory impairments in bipolar disorder are associated with functional and structural brain changes.

OBJECTIVES: We combined multimodal functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging to probe abnormalities in brain circuits underpinning episodic memory performance deficits in patients with bipolar disorder (BD). METHODS: We acquired whole-brain fMRI data in 21 patients with BD and a matched group of 20 healthy controls during a non-verbal episodic memory task, using abstract shapes. We also examined density of gray matter, using voxel-based morphometry (VBM), and integrity of connecting fiber tracts, using diffusion tensor imaging (DTI) and tract-based spatial statistics, for areas with significant activation differences. RESULTS: Patients with BD remembered less well than controls which shapes they had seen and had lower activation levels during the encoding stage of the task in the anterior cingulate gyrus, the precuneus/cuneus bilaterally, and the left lingual gyrus, and higher activation levels during the retrieval stage in the left temporo-parietal junction. Patients with BD showed reduced gray matter volumes in the left anterior cingulate, the precuneus/cuneus bilaterally, and the left temporo-parietal region in comparison with controls. DTI revealed increased radial, axial, and mean diffusivity in the left superior longitudinal fascicle in patients with BD compared with controls. CONCLUSIONS: Changes in task-related activation in frontal and parietal areas were associated with poorer episodic memory in patients with BD. Compared with data from single imaging modalities, integration of multimodal neuroimaging data enables the building of more complete neuropsychological models of mental disorders.

Frontal white matter alterations are associated with executive cognitive function in euthymic bipolar patients.

BACKGROUND: Bipolar affective disorder (BD) is often associated with cognitive dysfunction in executive domains. However the biological underpinnings of cognitive deficits in BD are not sufficiently understood. A growing body of evidence indicates a loss of microstructural integrity in various white matter (WM) fiber tracts in BD. The aim of the current study was to assess potential links between WM structural abnormalities and cognitive performance in euthymic middle-aged BD patients (n=30) and matched healthy controls (n=32). METHODS: Diffusion tensor imaging (DTI) data was carried out with both voxelwise (tract based spatial statistics, TBSS) and region-of-interest (ROI) based analysis. We compared multiple indices of diffusion including fractional anisotropy (FA), radial (DR), axial (DA) and mean diffusivities (MD). RESULTS: Increased mean diffusivity was found in the fornix, anterior thalamic radiation, splenium and the truncus of the corpus callosum in BD patients compared with controls. These diffusion changes were significantly associated with poorer performance in executive tasks in BD patients. CONCLUSIONS: Our results indicate a direct link between executive cognitive functioning and abnormal WM microstructural integrity of fronto-limbic tracts in remitted BD patients, and add evidence to the neuronal disruption that underlies the residual symptomatology of BD.

Differential effects of the ApoE4 genotype on brain structure and function.

The apolipoprotein E ε4 allele is a well established genetic risk factor for sporadic Alzheimer's disease. It is associated with structural and functional brain changes in healthy young, middle-aged and elderly subjects. In the current study, we assessed the impact of the ApoE genotype on brain macro- and microstructure, cognitive functioning and brain activity in fifty healthy young subjects (25 ApoE ε4 (ε4+) carriers and 25 non-carriers (ε4-), mean age 26.4±4.6years). We used diffusion tensor imaging (DTI) and voxel based morphometry (VBM) to assess brain structure, an extensive neuropsychological battery to test cognitive functioning and event-related functional magnetic resonance imaging (fMRI) to capture brain activity during episodic memory encoding and retrieval. ApoE ε4 carriers differed from non-carriers in fMRI activations but not in cognitive performance nor in brain micro- and macrostructure. These results suggest functional alterations in the episodic memory network that are modulated by the ε4 allele and might precede clinical or structural neurodegeneration.

Verbal episodic memory deficits in remitted bipolar patients: a combined behavioural and fMRI study.

BACKGROUND: Episodic memory deficits affect the majority of patients with bipolar disorder (BD). AIMS: The study investigates episodic memory performance through different approaches, including behavioural measures, physiological parameters, and the underlying functional activation patterns with functional neuroimaging (fMRI). METHODS: 26 Remitted BD patients and a matched group of healthy controls underwent a verbal episodic memory test together with monitored autonomic response, psychopathological ratings and functional magnetic resonance imaging (fMRI) during the verbal episodic memory test. RESULTS: Compared to healthy controls, BD patients performed significantly worse during the episodic memory task. The results further indicate that verbal episodic memory deficits in BD are associated with abnormal functional activity patterns in frontal, occipital and limbic regions, and an increase in stress parameters. LIMITATIONS: We aimed to minimise sample heterogeneity by setting clear criteria for remission, based on the scores of a depression (BDI II) and mania scale (BRMAS) and on the DSM IV criteria. However, our patients were not symptom-free and scored higher on BDI II scores than the control group. CONCLUSIONS: The results are of interest for the treatment of cognitive symptoms in BD patients, as persistent cognitive impairment may hamper full rehabilitation.

Altered intrinsic functional connectivity in language-related brain regions in association with verbal memory performance in euthymic bipolar patients.

Potential abnormalities in the structure and function of the temporal lobes have been studied much less in bipolar disorder than in schizophrenia. This may not be justified because language-related symptoms, such as pressured speech and flight of ideas, and cognitive deficits in the domain of verbal memory are amongst the hallmark of bipolar disorder (BD), and contribution of temporal lobe dysfunction is therefore likely. In the current study, we examined resting-state functional connectivity (FC) between the auditory cortex (Heschl's gyrus [HG], planum temporale [PT]) and whole brain using seed correlation analysis in n = 21 BD euthymic patients and n = 20 matched healthy controls and associated it with verbal memory performance. In comparison to controls BD patients showed decreased functional connectivity between Heschl's gyrus and planum temporale and the left superior and middle temporal gyrus. Additionally, fronto-temporal functional connectivity with the right inferior frontal/precentral gyrus and the insula was increased in patients. Verbal episodic memory deficits in the investigated sample of BD patients and language-related symptoms might therefore be associated with a diminished FC within the auditory/temporal gyrus and a compensatory fronto-temporal pathway.

Association between psychotic symptoms and cortical thickness reduction across the schizophrenia spectrum.

The current study provides a complete magnetic resonance imaging (MRI) analysis of thickness throughout the cerebral cortical mantle in patients with schizophrenia (SZ) and rigorously screened and matched unaffected relatives and controls and an assessment of its relation to psychopathology and subjective cognitive function. We analyzed 3D-anatomical MRI data sets, obtained at 3 T, from 3 different subject groups: 25 SZ patients, 29 first-degree relatives, and 37 healthy control subjects. We computed whole-brain cortical thickness using the Freesurfer software and assessed group differences. We also acquired clinical and psychometric data. The results showed markedly reduced cortical thickness in SZ patients compared with controls, most notably in the frontal and temporal lobes, in the superior parietal lobe and several limbic areas, with intermediate levels of cortical thickness in relatives. In both patients and relatives, we found an association between subjective cognitive dysfunction and reduced thickness of frontal cortex, and predisposition toward hallucinations and reduced thickness of the superior temporal gyrus. Our findings suggest that changes in specific cortical areas may predispose to specific symptoms, as exemplified by the association between temporal cortex thinning and hallucinations.

Association between white matter fiber integrity and subclinical psychotic symptoms in schizophrenia patients and unaffected relatives.

In this study, we investigate whether aberrant integrity of white matter (WM) fiber tracts represents a genetically determined biological marker of schizophrenia (SZ), and its relation with clinical symptoms. We collected brain DTI data from 28 SZ patients, 18 first-degree relatives and 22 matched controls and used voxel-based analysis with tract-based spatial statistics (TBSS) in order to compare fractional anisotropy (FA) between groups. Mean voxel-based FA values from the entire skeleton of each group were compared. We did a multiple regression analysis, followed by single post-hoc contrasts between groups. FA values were extracted from the statistically significant areas. The results showed significantly smaller FA values for SZ patients in comparison with controls in cortico-spinal tracts, in commissural fibers, in thalamic projections, in association fibers and in cingulum bundles. A significant increase of FA in SZ patients in comparison with healthy controls was only found in the arcuate fasciculus. Relatives had intermediate values between patients and controls which were deemed significant in the comparison to patients and controls in association fibers, arcuate fasciculus and cingulum bundles. Lower FA values in association fibers were significantly associated with predisposition toward hallucinations (in SZ patients and relatives), with higher PANSS scores of positive symptoms and with duration of illness (SZ patients). Our results suggest that clinical and subclinical presentations of psychotic symptoms are associated with aberrant integrity of multiple WM tracts. This association may represent an endophenotype of schizophrenia, since it is present in unaffected relatives as well. Such endophenotypes may serve as quantitative traits for future genetic studies and as candidate markers for early and preclinical identification of subjects at risk.

Patterns of autobiographical memory in bipolar disorder examined by psychometric and functional neuroimaging methods.

This is the first study to combine psychometric and functional neuroimaging methods to study altered patterns of autobiographical memory in bipolar disorder (BD). All participants were interviewed with an expanded version of the Bielefelder Autobiographical Memory Inventory (Bielefelder Autobiographisches Gedächtnis Inventar 2004;Lisse: Swets and Zeitlinger). We then acquired functional magnetic resonance imaging data during a task of individually designed autobiographical recall. Compared with healthy controls, BD patients reported a stronger emotionality of autobiographical memories and more frequent recollections of autobiographical events during their everyday life. Furthermore, they failed to deactivate areas in the cuneus and lingual gyrus and showed decreased activation in the inferior frontal and precentral areas compared with the control group. More frequent intrusions from a person's past, which had a neural correlate in the lack of deactivation in some default mode network areas in BD patients, may contribute to manic or depressive symptoms.

Biomarkers for major depression and its delineation from neurodegenerative disorders.

Major depressive disorders (MDD) are among the most debilitating diseases worldwide and occur with a high prevalence in elderly individuals. Neurodegenerative diseases (in particular Alzheimer's disease, AD) do also show a strong age-dependent increase in incidence and prevalence among the elderly population. A high number of geriatric patients with MDD show cognitive deficits and a very high proportion of AD patients present co-morbid MDD, which poses difficult diagnostic and prognostic questions. Especially in prodromal and in very early stages of AD, it is almost impossible to differentiate between pure MDD and MDD with underlying AD. Here, we give a comprehensive review of the literature on the current state of candidate biomarkers for MDD ("positive MDD markers") and briefly refer to established and validated diagnostic AD biomarkers in order to rule out underlying AD pathophysiology in elderly MDD subjects with cognitive impairments ("negative MDD biomarkers"). In summary, to date there is no evidence for positive diagnostic MDD biomarkers and the only way to delineate MDD from AD is to use "negative MDD" biomarkers. Because of this highly unsatisfactory current state of MDD biomarker research, we propose a research strategy targeting to detect and validate positive MDD biomarkers, which is based on a complex (genetic, molecular and neurophysiological) biological model that incorporates current state of the art knowledge on the pathobiology of MDD. This model delineates common pathways and the intersection between AD and MDD. Applying these concepts to MDD gives hope that positive MDD biomarkers can be successfully identified in the near future.